Myxococcus xanthus is a gram negative bacterium which undergoes a simple cycle of multicellular development. It is an experimentally attractive organism in which to study the role of cell-cell interactions in the regulation of gene expression. The obligatory involvement of intercellular communication during its developmental program is implicated by the behavior of several developmentally defective mutants. The research described in this proposal will focus on one group of mutants which apparently fail to produce an intercellular signal required for the expression of several developmentally induced genes. The objective of this study is to understand the nature of this signal and the mechanism by which it modifies gene expression. Classical genetics will be augmented by gene fusion and recombinant DNA technology to determine which genes are required for the cell's response to the signal and to identify the specific regulatory steps by which the signal controls gene expression. Mutations affecting regulatory sites within promoters regulated by the signal will be generated by oligonucleotide directed mutagenesis, and analyzed by DNA sequence analysis. The signal molecule itself will be purified and the biochemical consequences of its interaction with cells will be characterized. The long range goal of this research is to understand the means by which this organism coordinates the behavior of individual cells during multicellular activities. The problem of multicellular coordination is a fundamental problem in developmental biology. The information provided by this work may help to provide a framework for thinking about tissue interactions in more complex organisms. In this way it is hoped that this work may help us to understand situations in which intercellular coordination goes awry; situations which may in part lead to tragedies such as birth defects and malignancies.